Physiopathological implications of P2X and P2X receptors in regulation of glomerular hemodynamics in angiotensin II-induced hypertension.

Deleterious effects of purinergic P2X and P2X receptors (P2XRs) in ANG II-dependent hypertension include increased renal vascular resistance, and impaired autoregulation and pressure natriuresis. However, their specific effects on the determinants of glomerular hemodynamics remain incompletely delineated. To investigate the P2XR contributions to altered glomerular hemodynamics in hypertension, the effects of acute blockade of P2XR, P2XR, and P2XR with NF449, A438079, and PSB12054, respectively, were evaluated in ANG II-infused rats (435 ng·kg·min). P2XR or P2XR blockade reduced afferent (6.85 ± 1.05 vs. 2.37 ± 0.20 dyn·s·cm) and efferent (2.85 ± 0.38 vs. 0.99 ± 0.07 dyn·s·cm) arteriolar resistances, leading to increases in glomerular plasma flow (75.82 ± 5.58 vs. 206.7 ± 16.38 nl/min), ultrafiltration coefficient (0.0198 ± 0.0024 vs. 0.0512 ± 0.0046 nl·min·mmHg), and single-nephron glomerular filtration rate (22.73 ± 2.02 vs. 51.56 ± 3.87 nl/min) to near normal values. Blockade of P2XR did not elicit effects in hypertensive rats. In normotensive sham-operated rats, only the P2XR antagonist caused an increase plasma flow and single-nephron glomerular filtration rate, whereas the P2XR antagonist induced glomerular vasoconstriction that was consistent with evidence that P2XR stimulation increases release of nitric oxide from endothelial cells. Mean arterial pressure remained unchanged in both hypertensive and normotensive groups. Western blot analysis showed overexpression of P2XR, P2XR, and P2XR proteins in hypertensive rats. Whereas it has been generally assumed that the altered glomerular vascular resistances in ANG II hypertension are due to AT receptor-mediated vasoconstriction, these data indicate a predominant P2XR and P2XR control of glomerular hemodynamics in ANG II hypertension.